Recently, investigations in which I have taken part (Gordon, Huxley and Julian, J. Physiol. 184, 170, 1966; Julian, J. Physiol. 218, 117,1971) have begun to correlate the general performance of muscle, or its contractility, to its basic microscopic and molecular structure and biochemical functioning. My objective is to continue these kinds of investigations with the goal of discovering the basic laws governing muscle contractility. Muscle force, length, speed of shortening and stiffness will be related to the length of the sarcomere, the fundamental unit of muscle, and to the level of activation set by the fraction of myofibrillar regulating sites filled with calcium. We already know from the work of Gordon, Huxley and Julian cited above that the maximum force a muscle producers at fixed length depends on the number of myosin cross-bridges attached to actin sites. The woRk proposed here will make it possible to understand how the maximum speed of unloaded shortening and the force-velocity relation depend on the myosin cross-bridge and actin site interaction cycle. It will then be possible to establish how the regulation of contractility by calcium manifests itself in varying the force and speed properties of contracting muscle. It will also be possible to study the effects of wide ranging changes in sarcomere length on the force-velocity properties while holding the level of activation by calcium constant. The results obtained will provide the information required to formulate new laws regulating muscle contractility. Most heart muscle physiologists have assumed that the early ideas of how skeletal muscles work could be directly applied to heart muscle studies. Since we now know that many of these early ideas no longer apply to skeletal muscle, it can hardly be doubted that new studies of heart muscle contractility based on modern views of how skeletal muscles work will lead to a deeper understanding of the factors regulating heart muscle performance. This will make it possible to better understand what goes wrong in heart failure when the heart is no longer able to pump an adequate supply of blood, and should lead to the development of ways to either prevent or ameliorate heart failure. BIBLIOGRAPHIC REFERENCES: Fred J. Julian and Michael R. Sollins, variation of muscle stiffness with force at increasin (Text Truncated -Exceeds Capacity)